Role of Dietary Phytochemicals in Targeting Human miRNAs for Cancer Prevention and Treatment.

MicroRNAs (miRNAs - ~22 nucleotides) are a type of non-coding RNAs that are involved in post-transcriptional gene silencing. They are known to regulate gene expression in diverse biological processes, such as apoptosis, development, and differentiation. Several studies have demonstrated that cancer initiation and progression are highly regulated by miRNA expression. The nutrients present in the diet may regulate the different stages of carcinogenesis. Interestingly, plant-based foods, like fruits and vegetables, have been shown to play a significant role in cancer prevention. Phytochemicals are bioactive compounds derived from plant sources, and they have been shown to have antiinflammatory, antioxidant, and anticancer properties. Recent findings suggest that dietary phytochemicals, such as genistein, resveratrol, and curcumin, exert significant anticancer effects by regulating various miRNAs. In this review, we focus on the role of dietary phytochemicals in cancer prevention and treatment through the modulation of miRNA expression.

Non-Coding RNA as Biomarkers for Survival in Colorectal Cancer Patients.

Colorectal cancer (CRC) has a high incidence and fatality rate worldwide. It ranks second concerning death worldwide. Cancer patients are diagnosed with the disease at a later stage due to the absence of early diagnostic methods, which leads to increased death. With the help of recent advancements in the fields of diagnosis and therapy, the development of novel methods using new targets could be helpful for the long-term survival of CRC patients when CRC is detected early. However, the prognosis for the advanced stage of CRC is abysmal. New biomarkers are emerging as promising alternatives since they can be utilized for early detection of CRC, are simple to use, and are non-invasive. Non-coding RNAs (ncRNAs) have been seen to have an aberrant expression in the development of many malignancies, including CRC. In the past two decades, much research has been done on non-coding RNAs, which may be valuable as biomarkers and targets for antitumor therapy. Non-coding RNAs can be employed in detecting and treating CRC. Non-coding RNAs play an essential role in regulating gene expression. This article reviews ncRNAs and their expression levels in CRC patients that might qualify them as potential biomarkers. Various ncRNAs have been associated with CRC, such as microRNAs, long non-coding RNAs, circular RNAs, etc. The expression of these non-coding RNAs may provide insights into the stages of cancer and the prognosis of cancer patients and thus take proper preliminary measures to decrease cancer-related deaths.

Targeting colon cancer stem cells using novel doublecortin like kinase 1 antibody functionalized folic acid conjugated hesperetin encapsulated chitosan nanoparticles.

The cancer stem cell (CSC) hypothesis is an evolving oncogenesis concept. CSCs have a distinct ability to self-renew themselves and also give rise to a phenotypically diverse population of cells. Targeting CSCs represents a promising strategy for cancer treatment. Plant-derived compounds are potent in restricting the expansion of CSCs. DCLK1 has been already reported as a colon CSC specific marker. Nanoparticles can effectively inhibit multiple types of CSCs by targeting specific markers. We have synthesized DCLK1 functionalized folic acid conjugated hesperetin encapsulated chitosan nanoparticles (CFH-DCLK1), specifically to target CSCs. In this regard, we have performed proliferation assay, colony formation assay, cell migration assay, apoptosis assay, flow cytometry analysis, real-time RT- PCR and western blot analyses to determine the effect of CFH-DCLK1 and CFH nanoparticles in HCT116-colon cancer cells. In our study, we have determined the median inhibitory concentration (IC50) of CFH (47.8 µM) and CFH-DCLK1 (4.8 µM) nanoparticles in colon cancer cells. CFH-DCLK1 nanoparticles induced apoptosis and inhibited the migration and invasion of colon cancer cells. Real time PCR and western blot results have demonstrated that the treatment with CFH-DCLK1 nanoparticles significantly reduced the expression of CSC markers such as DCLK1, STAT1 and NOTCH1 compared to the CFH alone in HCT116 colon cancer cells. Finally, in the 3D spheroid model, CFH-DCLK1 nanoparticles significantly inhibited the colonosphere growth. Overall, our results highlight the effectiveness of CFH-DCLK1 nanoparticles in targeting the colon cancer cells and CSCs. This study would lead to the development of therapies targeting both cancer cells and CSCs simultaneously using nanoformulated drugs, which could bring changes in the current cancer treatment strategies.

Impact of native and external factors on exosome release: understanding reactive exosome secretion and its biogenesis.

Exosomes are minuscule vesicles secreted in the endolytic region of most mammalian cells. The release of exosomes from the cell engenders cell-to-cell signaling between cellular-compartments. The trading of exosomes between tumor and yonder cells plays a hypercritical role in tumor growth and progression. The exosome released from each tumor cell sequestrates a unique biogenetic pathway reflecting its cellular origin depending on the tumor type. However, treatment of tumor cells with certain physiological factors like drugs, chemotherapy, radiation, etc., enhance the release of exosomes and alters its biogenetic pathway compared with untreated tumor cells. In this review, we will discuss how the non-native physiological factors influence the release of exosomes and how these reactive exosomes orchestrate a unique patterning of a cargo sorting mechanism. We will also discuss the role of reactively secreted exosomes in mediating tumor metastasis, angiogenesis, and tumor progression.